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Title: Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [2] ;  [2] ;  [2] ;  [5] ;  [5] ;  [3] ;  [6] ;  [7] ;  [2] ;  [3] ;  [3] ;  [8] ;  [9] ;  [10] ;  [11] ;  [12] more »;  [13] ;  [2] « less
  1. Univ. of Tokyo (Japan). Dept. of Molecular Pathology; Univ. of Tokyo Hospital, Tokyo (Japan)
  2. Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine
  3. Univ. of Texas, Houston, TX (United States). M.D. Anderson Cancer Center
  4. Univ. of Texas Health Science Center at Houston, Houston, TX (United States). Brown Foundation Inst. of Molecular Medicine; Univ. of Texas, Houston, TX (United States). M.D. Anderson Cancer Center
  5. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division
  6. Oncothyreon, Seattle, WA (United States)
  7. Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials; Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
  8. Univ. of Tokyo (Japan). Dept. of Molecular Pathology
  9. Wayne State Univ., Detroit, MI (United States). Dept. of Biomedical Engineering
  10. Univ. of Tokyo (Japan). Dept. of Molecular Pathology; Univ. of Tokyo (Japan). Graduate School of Engineering, Dept. of Bioengineering
  11. Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center; Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials; Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Chemical and Nuclear Engineering
  12. Harvard Medical School and Dept. of Neurology, Boston, MA (United States). Beth Israel Deaconess Medical Center
  13. Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center; Univ. of New Mexico School of Medicine, Albuquerque, NM (United States). Division of Hematology/Oncology
Publication Date:
OSTI Identifier:
1263534
Grant/Contract Number:
DMS-1562068; 1U54CA149196; 1U54CA143907;7010-14 SCOR; NIH U01 CA151792- 01; R01U54CA143837; 1U54CA151668; P50 CA140388
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 7; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org:
USDOE; Japan Society for the Promotion of Science; National Science Foundation (NSF); National Inst. of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES photothermal therapy; phage display; nanoparticle; mathematical modeling; ligand receptor